Document Detail


Src inhibits midline axon crossing independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) receptor tyrosine phosphorylation.
MedLine Citation:
PMID:  23283343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The phylogenetically conserved Netrin family of chemoattractants signal outgrowth and attractive turning of commissural axons through the Deleted in Colorectal Carcinoma (DCC) family of receptors. Src family kinases are thought to be major signaling effectors of Netrin/DCC. In vertebrates, Src and the closely related Fyn kinases phosphorylate DCC and form a receptor-bound signaling complex leading to activation of downstream effectors. Here we show that, in the Drosophila embryonic CNS, Src kinases are dispensable for midline attraction of commissural axons. Consistent with this observation, tyrosine phosphorylation of the Netrin receptor DCC or its Drosophila ortholog, Frazzled, is not necessary for attraction to Netrin. Moreover, we uncover an unexpected function of Src kinases: inhibition of midline axon crossing through a novel mechanism. We propose that distinct signaling outputs must exist for midline axon crossing independent of Src kinases in commissural neurons.
Authors:
Michael P O'Donnell; Greg J Bashaw
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-12     Revised Date:  2013-08-29    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  305-14     Citation Subset:  IM    
Affiliation:
Cell and Molecular Biology Graduate Group and Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / metabolism*
Cell Movement / physiology*
Drosophila
Growth Cones / metabolism
Neurons / metabolism*
Phosphorylation
Receptors, Cell Surface / metabolism*
Signal Transduction / physiology*
src-Family Kinases / metabolism*
Grant Support
ID/Acronym/Agency:
5-T32-007516//PHS HHS; 5-T32-GM07229/GM/NIGMS NIH HHS; NS-046333/NS/NINDS NIH HHS; NS054739/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Cell Surface; 0/netrin receptors; EC 2.7.10.2/src-Family Kinases
Comments/Corrections

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